Our approach to investigate potential P-glycoprotein-related grapefruit juice-drug interactions, based upon categorization into P-gp substrates and non-P-gp substrates, clearly revealed that grapefruit juice exposure has a considerable, activating impact on the secretory efflux of P-gp substrates. We therefore suspect, and will begin to test in this application, that the activating effect of grapefruit juice on P-glycoprotein partially counteracts the CYP3A-inhibitory effects of grapefruit juice.